Recently there has been an increased interest in predictive, preventative, and particularly personalized medicine which requires diagnostic tests with higher fidelity, e.g., sensitivity and specificity. Lateral Flow Immunoassay (LFIA) devices incorporate such diagnostic test and is a well-established technology in Point-of-Care (POC) diagnostics. Low cost, relative ease of manufacture, long shelf life, and ease of use by the customer are some of the advantages that make LFIA's very attractive.
The basic principal of a Lateral Flow Immunoassay is shown in FIG. 1. During the early development of LFIA diagnostic devices, the main focus was primarily on qualitative systems which provide an easy yes or no answer. The best know qualitative lateral flow system is the pregnancy test.
Currently however, there is an increasing demand for more sensitive, quantitative and also multiplexing measurements which require the implementation of reader systems. As such, Lateral Flow Immunoassay Devices can be used in new markets and for new applications.
The capillary flow rate is very important for LFIA's because the effective concentration of an analyte in a sample decreases with the square of an increase in flow rate. For quantitative measurements of analytes this relationship is very important because the signal intensity directly correlates with the effective concentration. Thus, the flow speed of the sample across the analytical test line affects quantitative measurements for the analyte of interest. For example a sample viscosity change of 30%, within normal blood viscosity variation, will result in up to 70% signal variation.
The viscosity of different samples, for example blood samples, may vary significantly. The significant variation in viscosity of samples (and therefore the capillary flow rate) does not generally affect the performance of pregnancy tests; however, when a biomarker value, such as its concentration, is to be tested and compared to its previous values quantification of the analyte/biomarker is very important.
In LFIA's the flow of the sample through the membrane is driven by capillary forces. The pore size of the absorbent materials/membranes and the viscosity of the sample are two parameters that have a direct influence on the flow speed of the sample through the system. With respect to the flow speed/rate damage to the membrane of the LFIA during the manufacturing process will introduce multiple artifacts that adversely affect the flow behavior. For example, separation of the membrane from the backing (or adhesive tape) results in an unobstructed path for the sample to flow rapidly down the edge of the membrane. This will lead to a concave flow and artifacts in the measurement.
Printed electronics includes certain printing methods which allow the creation of circuits on a huge variety of substrates such as paper or textiles. Advantages of printed electronics are that they allow low-cost, high-volume, high-throughput production of electrical systems. Especially for small, inexpensive and disposable devices this technology can be very advantageous in improving reliability of quantitative diagnostic test using LFIA's. This makes printed electronics very attractive to the field of single use biosensors.
Jolke Perelaer et al., “Inkjet-printed silver tracks: low temperature curing and thermal stability investigation”, Journal of Materials Chemistry (2008), vol. 18, pp 3209-3215, describe inkjet printing of ink at low temperature. The possibility to print low temperature curing materials increases the amount of usable material on which the electrodes can be printed (for example printing on temperature sensitive nitrocellulose membranes). Other printing methods such as roll to roll printing and stamping are also possible.
Some other key factors that affect the signal produced in a lateral flow test include temperature and ionic strength (including pH) of the solution. Including sensors and actuators that measure and influence such conditions is also important in reducing variations in the signal generated.